Hydrochloric Acid → 2-Chloro-5-fluoronicotinic acid

Participants

Reaction Steps

Ethyl-2-chloro-5-fluoro-nicotinoate (50.4 g, 0.247 mol) (see reference J. Med. Chem., 1993, 36(18), 2676–88) was dissolved in tetrahydrofuran (350 ml) and a 2 M aqueous solution of lithium hydroxide (247 ml, 0.495 mol) added. The reaction mixture was stirred at room temperature for 3 days. The pH of the solution was reduced to pH1 by addition of 6 N hydrochloric acid and then extracted with dichloromethane (3 fold). The combined extracts were dried over anhydrous magnesium sulphate and the solvent removed in vacuo to give a solid which was triturated with diethyl ether and then dried in vacuo to give 2-chloro-5-fluoro nicotinic acid (40.56 g) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ=8.20 (1H, s), 8.62 (1H, s) ppm. LRMS (electrospray): m/z [M+H]+ 174.

Provenance & Evidence